Prefrontal electrophysiological biomarkers and mechanism-based drug effects in a rat model of alcohol addiction.

Patients with alcohol use disorder (AUD) who seek treatment show highly variable outcomes. A precision medicine approach with biomarkers responsive to new treatments is warranted to overcome this limitation. Promising biomarkers relate to prefrontal control mechanisms that are severely disturbed in AUD.

Manipulation of the nuclear envelope-associated protein SLAP during mammalian brain development affects cortical lamination and exploratory behavior.

Here, we report the first characterization of the effects resulting from the manipulation of Soluble-Lamin Associated Protein (SLAP) expression during mammalian brain development. We found that SLAP localizes to the nuclear envelope and when overexpressed causes changes in nuclear morphology and lengthening of mitosis. SLAP overexpression in apical progenitors of the developing mouse brain altered asymmetric cell division, neurogenic commitment and neuronal migration ultimately resulting in unbalance in the proportion of upper, relative to deeper, neuronal layers.

A multicentric consortium study demonstrates that dimethylarginine dimethylaminohydrolase 2 is not a dimethylarginine dimethylaminohydrolase.

Dimethylarginine dimethylaminohydrolase 1 (DDAH1) protects against cardiovascular disease by metabolising the risk factor asymmetric dimethylarginine (ADMA). However, the question whether the second DDAH isoform, DDAH2, directly metabolises ADMA has remained unanswered. Consequently, it is still unclear if DDAH2 may be a potential target for ADMA-lowering therapies or if drug development efforts should focus on DDAH2's known physiological functions in mitochondrial fission, angiogenesis, vascular remodelling, insulin secretion, and immune responses.

Supplement Treatment with NAC and Omega-3 Polyunsaturated Fatty Acids during Pregnancy Partially Prevents Schizophrenia-Related Outcomes in the Poly I:C Rat Model.

Background: Heightened levels of inflammation and oxidative stress are thought to be involved in the pathophysiology of schizophrenia. We aimed to assess whether intake of anti-inflammatory and anti-oxidant drugs during pregnancy prevents later schizophrenia-related outcomes in a neurodevelopmental rat model of this disorder.

Methods: Pregnant Wistar rats were injected with polyriboinosinic-polyribocytidilic acid (Poly I:C) or saline and subsequently treated with either N-acetyl cysteine (NAC) or omega-3 polyunsaturated fatty acids (PUFAs) until delivery.

Knock-out of the critical nitric oxide synthase regulator DDAH1 in mice impacts amphetamine sensitivity and dopamine metabolism.

The enzyme dimethylarginine dimethylaminohydrolase 1 (DDAH1) plays a pivotal role in the regulation of nitric oxide levels by degrading the main endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA). Growing evidence highlight the potential implication of DDAH/ADMA axis in the etiopathogenesis of several neuropsychiatric and neurological disorders, yet the underlying molecular mechanisms remain elusive. In this study, we sought to investigate the role of DDAH1 in behavioral endophenotypes with neuropsychiatric relevance.

Constitutively active STING causes neuroinflammation and degeneration of dopaminergic neurons in mice.

Stimulator of interferon genes (STING) is activated after detection of cytoplasmic dsDNA by cGAS (cyclic GMP-AMP synthase) as part of the innate immunity defence against viral pathogens. STING binds TANK-binding kinase 1 (TBK1). TBK1 mutations are associated with familial amyotrophic lateral sclerosis, and the STING pathway has been implicated in the pathogenesis of further neurodegenerative diseases.

Assessment of DDAH1 and DDAH2 Contributions to Psychiatric Disorders via In Silico Methods.

The contribution of nitric oxide synthases (NOSs) to the pathophysiology of several neuropsychiatric disorders is recognized, but the role of their regulators, dimethylarginine dimethylaminohydrolases (DDAHs), is less understood. This study's objective was to estimate DDAH1 and DDAH2 associations with biological processes implicated in major psychiatric disorders using publicly accessible expression databases. Since co-expressed genes are more likely to be involved in the same biologic processes, we investigated co-expression patterns with DDAH1 and DDAH2 in the dorsolateral prefrontal cortex in psychiatric patients and control subjects.

Former Training Relieves the Later Development of Behavioral Inflexibility in an Animal Model Overexpressing the Dopamine Transporter.

A range of dopamine-dominating neuropsychiatric disorders present with cognitive deficits. In accordance, the dopamine transporter overexpressing rat model (DAT-tg rat) displays cognitive deficits by means of behavioral inflexibility and learning disabilities. It remains to be investigated when cognitive deficits emerge, due to the inherent DA irregularities, during the life course of the DAT-tg rat and what may relieve symptoms.

Mice Display Synchronous Hindlimb Locomotion and a Ventrally Fused Lumbar Spinal Cord Caused by a Point Mutation in .

Identifying the spinal circuits controlling locomotion is critical for unravelling the mechanisms controlling the production of gaits. Development of the circuits governing left-right coordination relies on axon guidance molecules such as ephrins and netrins. To date, no other class of proteins have been shown to play a role during this process.

A Multimodal Neuroprosthetic Interface to Record, Modulate and Classify Electrophysiological Biomarkers Relevant to Neuropsychiatric Disorders.

Most mental disorders, such as addictive diseases or schizophrenia, are characterized by impaired cognitive function and behavior control originating from disturbances within prefrontal neural networks. Their often chronic reoccurring nature and the lack of efficient therapies necessitate the development of new treatment strategies. Brain-computer interfaces, equipped with multiple sensing and stimulation abilities, offer a new toolbox whose suitability for diagnosis and therapy of mental disorders has not yet been explored.

Divergent Dimethylarginine Dimethylaminohydrolase Isoenzyme Expression in the Central Nervous System.

The endogenous methylated derivative of ʟ-arginine, N,N-dimethyl-ʟ-arginine (asymmetric dimethylarginine, ADMA), an independent risk factor in many diseases, inhibits the activity of nitric oxide synthases and, consequently, modulates the availability of nitric oxide. While most studies on the biological role of ADMA have focused on endothelial and inducible nitric oxide synthases modulation and its contribution to cardiovascular, metabolic, and renal diseases, a role in regulating neuronal nitric oxide synthases and pathologies of the central nervous system is less understood. The two isoforms of dimethylarginine dimethylaminohydrolase (DDAH), DDAH1 and DDAH2, are thought to be the main enzymes responsible for ADMA catabolism.

mTOR inhibitor improves autistic-like behaviors related to Tsc2 haploinsufficiency but not following developmental status epilepticus.

Background: Tuberous sclerosis complex (TSC), a multi-system genetic disorder often associated with autism spectrum disorder (ASD), is caused by mutations of TSC1 or TSC2, which lead to constitutive overactivation of mammalian target of rapamycin (mTOR). In several Tsc1+/- and Tsc2+/- animal models, cognitive and social behavior deficits were reversed by mTOR inhibitors. However, phase II studies have not shown amelioration of ASD and cognitive deficits in individuals with TSC during mTOR inhibitor therapy.

Hybridization capture of larch (Larix Mill.) chloroplast genomes from sedimentary ancient DNA reveals past changes of Siberian forest.

Siberian larch (Larix Mill.) forests dominate vast areas of northern Russia and contribute important ecosystem services to the world. It is important to understand the past dynamics of larches in order to predict their likely response to a changing climate in the future.

Neurocognitive Dysfunctions and Their Therapeutic Modulation in Patients With Methamphetamine Dependence: A Pilot Study.

Aim: Methamphetamine (MA) abuse and dependence are increasing worldwide and are commonly associated with cognitive deficits. Some studies indicate that such impairments can improve if users become abstinent, but overall results remain inconclusive. Hence, we have performed a longitudinal case-control study investigating key surrogates for attention and impulsive decision-making before and after treatment.

Sensation seeking, impulsivity, and aggression moderate sex effects on adolescent laboratory binging.

Sex, comprising biological and gender-related distinctions, is a known risk factor for alcohol use disorders. Moreover, sensation seeking, impulsivity, and aggression have been found to predict binge drinking and to reflect behavioral disinhibition. We tested effects of these disinhibited traits on binging during intravenous alcohol self-administration (ivASA), a method that eliminates sex differences in the pharmacokinetics of alcohol.

Correction to: Biomarkers and neuromodulation techniques in substance use disorders.

[This corrects the article DOI: 10.1186/s42234-020-0040-0.].

Biomarkers and neuromodulation techniques in substance use disorders.

Addictive disorders are a severe health concern. Conventional therapies have just moderate success and the probability of relapse after treatment remains high. Brain stimulation techniques, such as transcranial Direct Current Stimulation (tDCS) and Deep Brain Stimulation (DBS), have been shown to be effective in reducing subjectively rated substance craving.

Effectiveness of the First German-Language Group Psychotherapy Manual to Accompany Short-Term Treatment in Methamphetamine Dependence.

Methamphetamine abuse is expanding in Europe, leading to a shortfall in medical care for related disorders in many regions. Research focusing on the effectiveness and feasibility of methamphetamine-specific treatment programs is scarce, especially in short-term settings. To this end, we treated 31 patients with methamphetamine dependence using a new group psychotherapy manual added to standard psychiatric care.

Metabolic state and value-based decision-making in acute and recovered female patients with anorexia nervosa.

Background: Patients with anorexia nervosa forgo eating despite emaciation and severe health consequences. Such dysfunctional decision-making might be explained by an excessive level of self-control, alterations in homeostatic and hedonic regulation, or an interplay between these processes. We aimed to understand value-based decision-making in anorexia nervosa and its association with the gut hormone ghrelin.

Genome-wide sequence information reveals recurrent hybridization among diploid wheat wild relatives.

Many conflicting hypotheses regarding the relationships among crops and wild species closely related to wheat (the genera Aegilops, Amblyopyrum, and Triticum) have been postulated. The contribution of hybridization to the evolution of these taxa is intensely discussed. To determine possible causes for this, and provide a phylogeny of the diploid taxa based on genome-wide sequence information, independent data were obtained from genotyping-by-sequencing and a target-enrichment experiment that returned 244 low-copy nuclear loci.

Dissociation of wanting and liking in the sucrose preference test in dopamine transporter overexpressing rats.

The predominant theory of mesolimbic dopamine function in recent years has been the incentive salience hypothesis, which describes the role of midbrain dopaminergic circuits as encoding 'wanting', but not 'liking' of rewards, resulting in a dissociation of the two functions. However, until now, this dissociation was only established in separate behavioural assays. Here, we propose that the Sucrose Preference Test (SPT), which has previously been used to measure 'liking', can actually be interpreted in terms of both 'wanting' and 'liking': while relative preference is a proxy for 'liking', we argue that absolute consumption of sucrose is indicative of 'wanting'.

Functional evolution of nodulin 26-like intrinsic proteins: from bacterial arsenic detoxification to plant nutrient transport.

Nodulin 26-like intrinsic proteins (NIPs) play essential roles in transporting the nutrients silicon and boron in seed plants, but the evolutionary origin of this transport function and the co-permeability to toxic arsenic remains enigmatic. Horizontal gene transfer of a yet uncharacterised bacterial AqpN-aquaporin group was the starting-point for plant NIP evolution. We combined intense sequence, phylogenetic and genetic context analyses and a mutational approach with various transport assays in oocytes and plants to resolve the transorganismal and functional evolution of bacterial and algal and terrestrial plant NIPs and to reveal their molecular transport specificity features.

Boron demanding tissues of Brassica napus express specific sets of functional Nodulin26-like Intrinsic Proteins and BOR1 transporters.

The sophisticated uptake and translocation regulation of the essential element boron (B) in plants is ensured by two transmembrane transporter families: the Nodulin26-like Intrinsic Protein (NIP) and BOR transporter family. Though the agriculturally important crop Brassica napus is highly sensitive to B deficiency, and NIPs and BORs have been suggested to be responsible for B efficiency in this species, functional information of these transporter subfamilies is extremely rare. Here, we molecularly characterized the NIP and BOR1 transporter family in the European winter-type cv.

Unleashing floret fertility in wheat through the mutation of a homeobox gene.

Floret fertility is a key determinant of the number of grains per inflorescence in cereals. During the evolution of wheat ( sp.), floret fertility has increased, such that current bread wheat () cultivars set three to five grains per spikelet.